Microtine rodents provide an excellent opportunity for investigating the hormonal and neuronal substrates underlying complex social behaviors such as affiliation. Microtus orchogaster typically inhabit the prairie grasslands of North America and exhibit high levels of affiliative behavior. M. orchogaster tend to nest in groups composed either of mating pairs or extended families and form long lasting social bonds with their mates. In contrast, a related species from the Rocky Mountain area, M. montanus, are asocial and tend not to nest in male-female pairs. Arginine vasopressin (AVP) appears to play a central role in the control of some aspects of affiliative behaviors in male M. orchogaster. The distribution of AVP receptor (subtype V1a) gene expression in the brain differs strikingly between these two species. It has been hypothesized that this species difference in vasopressin receptor gene expression may be related to the species differences in social behaviors. This application is designed to investigate the molelcular mechanisms which control species-specific gene expression by analyzing the structure of the V1a receptor gene in the two vole species. Further experiments will use transgenic technology to understand how species-specific vasopressin receptor gene expression is achieved. Finally, the relationship between vasopressin receptor gene expression and social behavior will be investigated using a novel transgenic approach; vasopression receptor gene expression will be manipulated in the asocial M. Montanus brain and the resulting changes in social behavior will be characterized. Investigating the molecular nature of species-specific gene expression will lead not only to a better understanding of the neuroendocrine bases for social behavior, but also may provide insight into the complex control of region specific gene expression in the mammalian brain which is of great clinical importance.